Cyclization of γ-hydroxybutyric acid (GHBA) as a strategy to enhance its signal in gas chromatography analysis

TL;DR

This paper shows that cyclizing γ-hydroxybutyric acid (GHBA) improves its detection in gas chromatography more effectively than other methods like silylation or methylation.

Contribution

A novel and effective cyclization method is proposed to enhance GHBA signal in gas chromatography.

Findings

Cyclization of GHBA significantly reduces its limit of detection compared to silylation or methylation.

GHBA's low GC signal is due to polycondensation into non-volatile polyester in the injector.

The cyclization method is simple and effective for reliable quantification in various matrices.

Abstract

The aim of this work is to investigate whether precyclization of γ-hydroxybutyric acid (GABA) allows for increasing its gas chromatography (GC) signal, and if so, is it a more effective way to increase the signal of this compound than its silylation or methylation?

Gas chromatography-mass spectrometry (GC–MS) and GC with flame ionization detection (GC-FID) response to GHBA before and after silylation, methylation, and cyclization were compared. The impact of injector temperature on GHBA and γ-butyrolactone (GBL) signals was assessed. Fourier transformed infra-red spectroscopy was used to examine the formation of macromolecular derivatives in the injector.

GHBA shows a lower GC signal than GBL due to partial polycondensation into a non-volatile polyester in the injector. Validation data were established for GHBA after each derivatization. Silylation and methylation reduced the limit of detection (LOD) by approximately 1.5- and 1.3-fold, respectively, whereas pre-cyclization led to at least a 4.6-fold decrease in LOD.

The present study elucidates the reasons behind the low GHBA signal observed in GC analysis and, consequently, supports the recommendation to perform pre-cyclization of this compound prior to analysis. Furthermore, the findings demonstrate that although signal enhancement of GHBA can be achieved through silylation or methylation, the most substantial increase is observed following its cyclization during sample preparation. The proposed in this paper cyclization procedure is both remarkably simple and highly effective, allowing for reliable quantification of this hydroxycarboxylic acid in a variety of matrices, including plasma, urine, wine, beer, and orange juice.

The online version contains supplementary material available at 10.1007/s11419-025-00738-z.

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